A series of studies is proposed in subjects with histories of drug abuse and in normal human volunteers to investigate several effects that caffeine shares with classic stimulant drugs of abuse. A series of eleven studies will focus on the comparative clinical pharmacology of caffeine, nicotine and cocaine administered intravenously to stimulant drug abusers on a residential research laboratory. A set of four studies will evaluate the comparative intravenous reinforcing effects of caffeine, nicotine and cocaine. A second set of sour studies will examine interactions between acutely and chronically administered caffeine, nicotine and cocaine. Finally, a set of three studies will examine the effects of a selective dopaminergic blocker on the effects of intravenous caffeine, nicotine and cocaine. Concurrent with the residential studies, a series of non-residential studies in normal volunteers will investigate caffeine physical dependence and reinforcement. One study will explore the use of cerebral blood flow velocity and quantitative EEG as sensitive physiological measures of caffeine withdrawal. Two studies will explore pharmacological mechanisms in caffeine withdrawal by evaluating the effects of an adenosine-mediate challenge drug on caffeine withdrawal and by comparing the effects of caffeine, theophylline and methylphenidate on caffeine withdrawal. Another study will investigate graded dose reduction as a procedure for reducing severity of caffeine withdrawal. Finally, two studies will use choice procedures to compare the reinforcing effects of oral caffeine and d-amphetamine, explore correlates of individual differences in caffeine and d-amphetamine choice, and investigate whether acquisition of a caffeine discrimination enhances subsequent choice of caffeine. Given the widespread elicit use of physical dependence and reinforcement of the general population and in developing caffeine-use reduction or cessation programs as well as programs for minimizing caffeine-associated health risks. This research with caffeine and other classic psychomotor stimulants should also advance our understanding of pharmacological and behavioral mechanisms underlying stimulant drug abuse as well as provide novel information about interactions among commonly used and abused stimulants.